Project Summary The need for efficient methods to construct chiral building blocks has been increasing significantly over the last 20 years because of the implementation of regulatory guidelines regarding the creation of new stereodefined drugs. While hydrogenative transformations of ?-keto esters are well established and used extensively in industry to provide over 100 tons of material annually, asymmetric and chemoselective transformations with ?,?-unsaturated ?-ketoesters remain underexplored due to their diverse functionality and unconventional electronic biases. This proposal aims to develop practical catalytic reactions that take advantage of the high tunability of ligated copper species to selectively functionalize one of the three possible electrophilic sites in these molecules chemo- and stereoselectively. These methods will provide access to highly diversifiable enantioenriched secondary and tertiary allylic alcohols containing two contiguous stereocenter and a carboxylate moiety, and will expand the synthetic utility of ?-dicarbonyl compounds by exploiting their potential electrophilicity towards other nucleophiles. Aligning with our interest in accessing structurally complex and biologically relevant natural products, we are proposing a tunable and convergent approach that will provide access to unnatural variants of the Veratrum alkaloid jervine. Our strategy involves a diastereoselective conjugate addition of a complex steroid fragment with a stereochemically dense alkaloidal tricycle.